There is an increasing demand in the cosmetics industry to develop products that may be applied topically to the skin that improve the condition and appearance of skin. Consumers are interested in mitigating or delaying the dermatological signs of chronologically- or hormonally-aged skin, as well as skin aging due to environmental stress, such as fine lines, wrinkles, sagging skin and other conditions due to a progressive loss of cell growth, proliferation and functionality in the epidermal and dermal skin layers. During the aging process, the complexion of the skin, i.e., the color and appearance of the skin, deteriorates slowly from aging and/or prolonged exposure to environmental stress, e.g., sunlight. Numerous cosmetic and medical treatments have been developed in an attempt to treat environmentally damaged, aging or aged skin. However, such cosmetics or treatments commonly contain organic acids as their active ingredients or components, and are frequently associated with consumer discomfort, such as burning, itching, and redness.
Numerous means for obtaining a white or pale complexion are known and include skin lightening creams, bleaches, peels, and oral and injectable medication. Many of the known active ingredients include alpha hydroxy acids, kojic acid, ascorbic acid, hydroquinone, and glutathione, in addition to natural extracts, licorice, Glycyrrhiza glabra, arbutin, bearberry, Chlorella vulgaris extract, Perilla extract, and coconut fruit extract, as well as derivatives of any of the previously mentioned active ingredients. These and other known lightening products work in various ways. Some are based on inhibiting the production of melanin, which is responsible for pigmentation, eg. thiodipropionic acid, such as described in US Patent Application Publication Serial No. 2004/0126344, herein incorporated in its entirety for all purposes. Others are acids that remove old skin by promoting exfoliation, for example, alpha hydroxyl acids. Although many of these lightening agents do work, many may have serious side effects.
Some of the side effects of lightening agents include, but are not limited to: redness, itching, stinging, burning, crusting, swelling, unusual discoloration, and more serious side effects such as ochronosis, i.e., the appearance of very dark patches of skin that are difficult to remove. Leukoderma, where the skin loses the ability to produce pigment altogether, resulting in patches of pink, may also result from using some known lighteners.
DICKKOPF-1, which is a protein that is highly expressed in dermal fibroblasts of human skin on the palms and soles, has been shown to have a paracrine action on melanocytes, inhibiting the function and proliferation of melanocytes in epidermis; this is believed to be one of the mechanisms controlling pigmentation on palmo-plantar skin. (J. Cell Biol. 2004 Apr. 26; 165(2):275-85, J Invest Dermatol. 2007 May; 127(5):1217-25. FASEB J. 2008 April; 22(4):1009-20, J Investig Dermatol Symp Proc. 2009 August; 14(1):73-5). U.S. Pat. No. 8,198,244 describes topically administering DICKKOPF-1 to increase skin thickness, decrease skin pigmentation, and/or reduce hair growth.
Clintonia borealis (C. borealis), more commonly referred to as the Bluebeard Lily, is found in the eastern to central North American regions. This perennial plant grows up to 12 inches in height, with leathery, shiny leaves, blue berries and yellow bell-like flowers on a tall leafless stalk that is in full bloom from May-July. Native American Indians, such as the Potawatami and Algonquins, used Clintonia for a number of medicinal purposes. For example, fresh poulticed leaves were applied topically to burns, sores, bruises and rabid animal bites for the plant's anti-inflammatory properties. The root of the plant was used to ease childbirth, and Arch Chemicals has subsequently prepared an extract from the roots of C. borealis marketed as NAB® Clintonia Borealis. JP 2003306424 describes cosmetics containing Uvularia extracts (including C. borealis) for enhancing activities of skin-lightening agents. JP 2003292416 A describes a skin external agent containing extractive solution of plant of C. borealis with effects in moistening skin and preventing pachylosis and pigmentation, and includes a working example of an ethanolic extraction of C. borealis. 
Many of the physiological processes in play in the development of undesirable skin or hair have counterparts in eukaryotic microorganisms, such as yeast, and yeast extracts have been used in cosmetic applications. For example, in response to heat, UV radiation, or other stress, yeast are known to produce factors that promote cell proliferation or viability. See, e.g., U.S. Pat. No. 2,239,345. Stressed yeast lysates containing such factors have been described and have been indicated for use in cosmetic applications directed to counteracting the effects of certain stresses on the skin. For example, UV-stressed yeast lysates have been used in cosmetic applications. See, e.g., U.S. Pat. Nos. 5,643,587; 5,676,956; and 5,776,441. More recently, ozone-stressed yeast lysates have been described as useful in protecting skin cells from the harmful effects of ozone. See, e.g., U.S. Pat. Nos. 6,461,857 and 6,858,212 to Scholz et al; and U.S. Pat. Appl. Pub. Nos. 2003/0198682 and 2006/0110815. U.S. Pat. Appl. Pub. No. 2010/0021532 describes a yeast/polyphenol ferment extract that contains new actives beneficial to the skin, wherein the new actives result from a yeast belonging to the genus of Pichia being exposed to a non-cytotoxic amount of a polyphenol as a growth factor during a key stage of fermentation. Nonetheless, these earlier cases failed to recognize certain cosmetic uses and failed to identify active ingredients within the cellular lysates.
The foregoing discussion is presented solely to provide a better understanding of nature of the problems confronting the art and should not be construed in any way as an admission as to prior art nor should the citation of any reference herein be construed as an admission that such reference constitutes “prior art” to the instant application.